Current research is showing involvement of mitochondria in a variety of pathological situations. Inherited mitochondrial diseases show a unique maternal inheritance characterized by partial penetrance and heteroplasmy among the tissues. Mitochondrial DNA mutations may accumulate with age due to inadequate repair and turnover. In several instances of necrotic cell death caused by hypoxia/ischemia or chemical toxicity, opening of high conductance permeability transition pores in the mitochondrial inner membrane has been shown to lead to mitochondrial depolarization, release of ions, uncoupling of oxidative phosphorylation, permeation of solutes and, ultimately, cell killing. Onset of this mitochondrial permeability transition also activates the machinery for apoptosis. Release of cytochrome c after onset of the mitochondrial permeability transition activates proteases and endonucleases of the apoptotic program. The anti-apoptotic gene, Bcl-2, encodes a protein that localizes to mitochondria and prevents onset of the mitochondrial permeability transition. Inherited and acquired defects of the mitochondrial genome are linked to impaired mitochondrial energy production, increased mitochondrial free radical generation and cell death in aging, neurodegenerative diseases and maternally inherited mitochondrial disorders. These examples illustrate how mitochondrial dysfunction underlies a wide spectrum of disease. Understanding of the basic mechanisms underlying mitochondrial dysfunction can lead to a better understanding of pathophysiologic processes and new strategies for prevention and treatment. The purpose of this conference is to bring together leading researchers studying mitochondrial dysfunction in many different disease settings to share ideas and recent research findings.